Rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterised risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and use of conventional, biological, and newz non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favourable, many still do not respond to current therapies. Accordingly, new therapies are urgently required. In this Seminar, we describe current insights into genetics and aetiology, pathophysiology, epidemiology, assessment, therapeutic agents, and treatment strategies together with unmet needs of patients with rheumatoid arthritis

Developments in the clinical understanding of rheumatoid arthritis

The changes occurring in the field of rheumatoid arthritis (RA) over the past decade or two have encompassed new therapies and, in particular, a new look at the clinical characteristics of the disease in the context of therapeutic improvements. It has been shown that composite disease activity indices have special merits in following patients, that disease activity governs the evolution of joint damage, and that disability can be dissected into several components – among them disease activity and joint damage. It has also been revealed that aiming at any disease activity state other than remission (or, at worst, low disease activity) is associated with significant progression of joint destruction, that early recognition and appropriate therapy of RA are important facets of the overall strategy of optimal clinical control of the disease, and that tight control employing composite scores supports the optimization of the therapeutic approaches. Finally, with the advent of novel therapies, remission has become a reality and the treatment algorithms encompassing all of the above-mentioned aspects will allow us to achieve the rigorous aspirations of today and tomorrow

Synchronization of Coupled Nonidentical Genetic Oscillators

The study on the collective dynamics of synchronization among genetic oscillators is essential for the understanding of the rhythmic phenomena of living organisms at both molecular and cellular levels. Genetic oscillators are biochemical networks, which can generally be modelled as nonlinear dynamic systems. We show in this paper that many genetic oscillators can be transformed into Lur'e form by exploiting the special structure of biological systems. By using control theory approach, we provide a theoretical method for analyzing the synchronization of coupled nonidentical genetic oscillators. Sufficient conditions for the synchronization as well as the estimation of the bound of the synchronization error are also obtained. To demonstrate the effectiveness of our theoretical results, a population of genetic oscillators based on the Goodwin model are adopted as numerical examples.Comment: 16 pages, 3 figure

Individual differences in EEG correlates of recognition memory due to DAT polymorphisms

Introduction Although previous research suggests that genetic variation in dopaminergic genes may affect recognition memory, the role dopamine transporter expression may have on the behavioral and EEG correlates of recognition memory has not been well established. Objectives The study aims to reveal how individual differences in dopaminergic functioning due to genetic variations in the dopamine transporter gene influences behavioral and EEG correlates of recognition memory. Methods Fifty‐eight participants performed an item recognition task. Participants were asked to retrieve 200 previously presented words while brain activity was recorded with EEG. Regions of interest were established in scalp locations associated with recognition memory. Mean ERP amplitudes and event‐related spectral perturbations when correctly remembering old items (hits) and recognizing new items (correct rejections) were compared as a function of dopamine transporter group. Results Participants in the dopamine transporter group that codes for increased dopamine transporter expression (10/10 homozygotes) display slower reaction times compared to participants in the dopamine transporter group associated with the expression of fewer dopamine transporters (9R‐carriers). 10/10 homozygotes further displayed differences in ERP and oscillatory activity compared to 9R‐carriers. 10/10 homozygotes fail to display the left parietal old/new effect, an ERP signature of recognition memory associated with the amount of information retrieved. 10/10 homozygotes also displayed greater decreases of alpha and beta oscillatory activity during item memory retrieval compared to 9R‐carriers. Conclusion Compared to 9R‐carriers, 10/10 homozygotes display slower hit and correct rejection reaction times, an absence of the left parietal old/new effect, and greater decreases in alpha and beta oscillatory activity during recognition memory. These results suggest that dopamine transporter polymorphisms influence recognition memory